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Hypertrophic Scars and Keloids: Advances in Treatment and Review of Established Therapies

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Abstract

Hypertrophic scars and keloids can have significant detrimental effects on patients both psychosocially and functionally. A careful identification of patient risk factors and a comprehensive management plan are necessary to optimize outcomes. Patients with a history of dystrophic scarring should avoid unnecessary procedures and enhance the wound-healing process using various preventive strategies. As there is no single, fully efficacious treatment modality, prevention remains the best approach in reducing aberrant scar formation. When prevention therapies fail, keloids have been shown to be respond to a variety of therapies including topical and injectable corticosteroids, 5-fluorouracil, radiotherapy, lasers, and surgical excision, all with varying efficacies. As such, management should be tailored to the individual patient’s risk factors with the use of combination therapies to reduce recurrence rates. Still, keloid and hypertrophic scar therapies are widely diverse with novel treatment modalities providing alternatives for recurring lesions. Laser-assisted drug delivery, skin priming, and novel topical therapies may provide alternative options for the management of hypertrophic scars and keloids.

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References

  1. Ghazawi FM, Zargham R, Gilardino MS, Sasseville D, Jafarian F. Insights into the pathophysiology of hypertrophic scars and keloids: how do they differ? Adv Skin Wound Care. 2018;31(1):582–95.

    Article  PubMed  Google Scholar 

  2. Feng Y, Wu JJ, Sun ZL, Liu SY, Zou ML, Yuan ZD, et al. Targeted apoptosis of myofibroblasts by elesclomol inhibits hypertrophic scar formation. EBioMedicine. 2020;54: 102715.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Elsaie ML. Update on management of keloid and hypertrophic scars: a systemic review. J Cosmet Dermatol. 2021;20(9):2729–38.

    Article  PubMed  Google Scholar 

  4. Darby IA, Desmoulière A. Scar formation: cellular mechanisms. In: Téot L, Mustoe TA, Middelkoop E, Gauglitz GG, editors. Textbook on scar management: state of the art management and emerging technologies. Cham: Springer International Publishing; 2020. p. 19–26.

    Chapter  Google Scholar 

  5. Hoffmann A, Hoing JL, Newman M, Simman R. Role of hyaluronic acid treatment in the prevention of keloid scarring. 2013.

  6. Lee HJ, Jang YJ. Recent understandings of biology, prophylaxis and treatment strategies for hypertrophic scars and keloids. Int J Mol Sci. 2018;19:3.

    Google Scholar 

  7. Gianatasio C, Abrouk M, Waibel JS. Treatment approaches for treating hypertrophic scars and keloids. Dermatol Rev. 2021;2(1):11–22.

    Article  Google Scholar 

  8. Armour A, Scott PG, Tredget EE. Cellular and molecular pathology of HTS: basis for treatment. Wound Repair Regen. 2007;159(1):S6–17.

    Article  Google Scholar 

  9. Scott PG, Dodd CM, Tredget EE, Ghahary A, Rahemtulla F. Chemical characterization and quantification of proteoglycans in human post-burn hypertrophic and mature scars. Clin Sci (Lond). 1996;90(5):417–25.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang Z, Li XJ, Liu Y, Zhang X, Li YY, Xu WS. Recombinant human decorin inhibits cell proliferation and downregulates TGF-beta1 production in hypertrophic scar fibroblasts. Burns. 2007;33(5):634–41.

    Article  PubMed  Google Scholar 

  11. Ogawa R. The most current algorithms for the treatment and prevention of hypertrophic scars and keloids: a 2020 update of the algorithms published 10 years ago. Plast Reconstr Surg. 2022;149(1):79e–94e.

    Article  CAS  PubMed  Google Scholar 

  12. Juckett G, Hartman-Adams H. Management of keloids and hypertrophic scars. Am Fam Physician. 2009;80(3):253–60.

    PubMed  Google Scholar 

  13. Jfri A, Alajmi A. Spontaneous keloids: a literature review. Dermatology. 2018;234(3–4):127–30.

    Article  PubMed  Google Scholar 

  14. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17(1–2):113–25.

    Article  CAS  PubMed  Google Scholar 

  15. Limandjaja GC, Niessen FB, Scheper RJ, Gibbs S. Hypertrophic scars and keloids: overview of the evidence and practical guide for differentiating between these abnormal scars. Exp Dermatol. 2021;30(1):146–61.

    Article  CAS  PubMed  Google Scholar 

  16. Ogawa R, Okai K, Tokumura F, Mori K, Ohmori Y, Huang C, et al. The relationship between skin stretching/contraction and pathologic scarring: the important role of mechanical forces in keloid generation. Wound Repair Regen. 2012;20(2):149–57.

    Article  PubMed  Google Scholar 

  17. Atkinson JA, McKenna KT, Barnett AG, McGrath DJ, Rudd M. A randomized, controlled trial to determine the efficacy of paper tape in preventing hypertrophic scar formation in surgical incisions that traverse Langer’s skin tension lines. Plast Reconstr Surg. 2005;116(6):1648–56.

    Article  CAS  PubMed  Google Scholar 

  18. Arno AI, Gauglitz GG, Barret JP, Jeschke MG. Up-to-date approach to manage keloids and hypertrophic scars: a useful guide. Burns. 2014;40(7):1255–66.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ibrahim NE, Shaharan S, Dheansa B. Adverse effects of pregnancy on keloids and hypertrophic scars. Cureus. 2020;12(12): e12154.

    PubMed  PubMed Central  Google Scholar 

  20. Moustafa MF, Abdel-Fattah MA, Abdel-Fattah DC. Presumptive evidence of the effect of pregnancy estrogens on keloid growth: case report. Plast Reconstr Surg. 1975;56(4):450–3.

    Article  CAS  PubMed  Google Scholar 

  21. Macarak EJ, Wermuth PJ, Rosenbloom J, Uitto J. Keloid disorder: fibroblast differentiation and gene expression profile in fibrotic skin diseases. Exp Dermatol. 2021;30(1):132–45.

    Article  CAS  PubMed  Google Scholar 

  22. Chike-Obi CJ, Cole PD, Brissett AE. Keloids: pathogenesis, clinical features, and management. Semin Plast Surg. 2009;23(3):178–84.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hellwege JN, Russell SB, Williams SM, Edwards TL, Velez Edwards DR. Gene-based evaluation of low-frequency variation and genetically-predicted gene expression impacting risk of keloid formation. Ann Hum Genet. 2018;82(4):206–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nakashima M, Chung S, Takahashi A, Kamatani N, Kawaguchi T, Tsunoda T, et al. A genome-wide association study identifies four susceptibility loci for keloid in the Japanese population. Nat Genet. 2010;42(9):768–71.

    Article  CAS  PubMed  Google Scholar 

  25. Tulandi T, Al-Sannan B, Akbar G, Ziegler C, Miner L. Prospective study of intraabdominal adhesions among women of different races with or without keloids. Am J Obstet Gynecol. 2011;204(2):132.e1-4.

    Article  PubMed  Google Scholar 

  26. Young WG, Worsham MJ, Joseph CL, Divine GW, Jones LR. Incidence of keloid and risk factors following head and neck surgery. JAMA Facial Plast Surg. 2014;16(5):379–80.

    Article  PubMed  Google Scholar 

  27. Lu YY, Lu CC, Yu WW, Zhang L, Wang QR, Zhang CL, et al. Keloid risk in patients with atopic dermatitis: a nationwide retrospective cohort study in Taiwan. BMJ Open. 2018;8(7): e022865.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Diaz A, Tan K, He H, Xu H, Cueto I, Pavel AB, et al. Keloid lesions show increased IL-4/IL-13 signaling and respond to Th2-targeting dupilumab therapy. J Eur Acad Dermatol Venereol. 2020;34(4):e161–4.

    Article  CAS  PubMed  Google Scholar 

  29. Tirgan MH, Uitto J. Lack of efficacy of dupilumab in the treatment of keloid disorder. J Eur Acad Dermatol Venereol. 2022;36(2):e120–2.

    Article  CAS  PubMed  Google Scholar 

  30. Bran GM, Goessler UR, Hormann K, Riedel F, Sadick H. Keloids: current concepts of pathogenesis (review). Int J Mol Med. 2009;24(3):283–93.

    Article  CAS  PubMed  Google Scholar 

  31. El Kinani M, Duteille F. Scar epidemiology and consequences. In: Téot L, Mustoe TA, Middelkoop E, Gauglitz GG, editors. Textbook on scar management: state of the art management and emerging technologies. Cham: Springer International Publishing; 2020. p. 45–9.

    Chapter  Google Scholar 

  32. Taylor SC. Epidemiology of skin diseases in ethnic populations. Dermatol Clin. 2003;21(4):601–7.

    Article  PubMed  Google Scholar 

  33. Rockwell WB, Cohen IK, Ehrlich HP. Keloids and hypertrophic scars: a comprehensive review. Plast Reconstr Surg. 1989;84(5):827–37.

    Article  CAS  PubMed  Google Scholar 

  34. Gangemi EN, Gregori D, Berchialla P, Zingarelli E, Cairo M, Bollero D, et al. Epidemiology and risk factors for pathologic scarring after burn wounds. Arch Facial Plast Surg. 2008;10(2):93–102.

    Article  PubMed  Google Scholar 

  35. Kruglikov IL, Scherer PE. Caveolin-1 as a target in prevention and treatment of hypertrophic scarring. NPJ Regen Med. 2019;4:9.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Rumsey N, Clarke A, White P. Exploring the psychosocial concerns of outpatients with disfiguring conditions. J Wound Care. 2003;12(7):247–52.

    Article  CAS  PubMed  Google Scholar 

  37. Tripathi S, Soni K, Agrawal P, Gour V, Mondal R, Soni V. Hypertrophic scars and keloids: a review and current treatment modalities. Biomed Dermatol. 2020;4(1):1–11.

    Article  Google Scholar 

  38. Ogawa R, Dohi T, Tosa M, Aoki M, Akaishi S. The latest strategy for keloid and hypertrophic scar prevention and treatment: the Nippon Medical School (NMS) Protocol. J Nippon Med School. 2021;88(1):2–9.

    Article  CAS  Google Scholar 

  39. Levenson SM, Geever R EF, Crowley LV, Oates JF 3rd, Berard CW, Rosen H. The Healing Of Rat Skin Wounds. Ann Surg. 1965;161(2):293-308.

  40. Sarrazy V, Billet F, Micallef L, Coulomb B, Desmoulière A. Mechanisms of pathological scarring: Role of myofibroblasts and current developments. Wound Repair Regen. 2011;19:10–5.

    Article  Google Scholar 

  41. Tan ST, Winarto N, Dosan R, Aisyah PB. The benefits of occlusive dressings in wound healing. Open Dermatol J. 2019;13(1):27–33.

    Article  CAS  Google Scholar 

  42. Mustoe TA, Gurjala A. The role of the epidermis and the mechanism of action of occlusive dressings in scarring. Wound Repair Regen. 2011;19 Suppl 1(0 1):s16-21.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hutchinson JJ, McGuckin M. Occlusive dressings: a microbiologic and clinical review. 1990.

  44. de Oliveira GV, Gold MH. Silicone sheets and new gels to treat hypertrophic scars and keloids: A short review. Dermatol Ther. 2020;33(4):e13705.

  45. Perkins K, Davey RB, Wallis KA. Silicone gel: a new treatment for burn scars and contractures. Burns Incl Therm Inj. 1983;9(3):201–4.

    Article  CAS  PubMed  Google Scholar 

  46. O'Shaughnessy KD, De La Garza M, Roy NK, Mustoe TA. Homeostasis of the epidermal barrier layer: a theory of how occlusion reduces hypertrophic scarring. Wound Repair Regen. 2009;17(5):700-8.

  47. De Decker I, Hoeksema H, Verbelen J, Vanlerberghe E, De Coninck P, Speeckaert MM, et al. The use of fluid silicone gels in the prevention and treatment of hypertrophic scars: a systematic review and meta-analysis. Burns. 2022;48(3):491–509.

    Article  PubMed  Google Scholar 

  48. Wiseman J, Ware RS, Simons M, McPhail S, Kimble R, Dotta A, et al. Effectiveness of topical silicone gel and pressure garment therapy for burn scar prevention and management in children: a randomized controlled trial. Clin Rehabil. 2020;34(1):120–31.

    Article  PubMed  Google Scholar 

  49. Jenwitheesuk K, Surakunprapha P, Kuptarnond C, Prathanee S, Intanoo W. Role of silicone derivative plus onion extract gel in presternal hypertrophic scar protection: a prospective randomized, double blinded, controlled trial. Int Wound J. 2012;9(4):397–402.

    Article  PubMed  Google Scholar 

  50. de Giorgi V, Sestini S, Mannone F, Papi F, Alfaioli B, Gori A, et al. The use of silicone gel in the treatment of fresh surgical scars: a randomized study. Clin Exp Dermatol. 2009;34(6):688–93.

    Article  PubMed  Google Scholar 

  51. Shirazi M, Mohammadi AA, Shamohammadi I, Mahboubi A, Makarem A. Efficacy of silicone gel in reducing scar formation after hypospadias repair: a randomized placebo-controlled trial. Res Rep Urol. 2019;11:291–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. van der Wal MBA, van Zuijlen PP, van de Ven P, Middelkoop E. Topical silicone gel versus placebo in promoting the maturation of burn scars: a randomized controlled trial. Plast Reconstr Surg. 2010;126(2):524–31.

    Article  PubMed  Google Scholar 

  53. Gold MH, Andriessen A, Dayan SH, Fabi SG, Lorenc ZP, Henderson Berg MH. Hypochlorous acid gel technology: its impact on postprocedure treatment and scar prevention. J Cosmet Dermatol. 2017;16(2):162–7.

    Article  PubMed  Google Scholar 

  54. Bucko AD DZ, Dubois JC, Jones TM. A double-blind, randomized study to compare microcyn scar management hydrogel, K103163, and Kelo-cote scar gel for hypertrophic or keloid scars. In: Poster presented at: 14th Annual Caribbean Dermatology Symposium, 20–24; 2020.

  55. Pangkanon W, Yenbutra P, Kamanamool N, Tannirandorn A, Udompataikul M. A comparison of the efficacy of silicone gel containing onion extract and aloe vera to silicone gel sheets to prevent postoperative hypertrophic scars and keloids. J Cosmet Dermatol. 2021;20(4):1146–53.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Wananukul S, Chatpreodprai S, Peongsujarit D, Lertsapcharoen P. A prospective placebo-controlled study on the efficacy of onion extract in silicone derivative gel for the prevention of hypertrophic scar and keloid in median sternotomy wound in pediatric patients. J Med Assoc Thai. 2013;96(11):1428–33.

    PubMed  Google Scholar 

  57. O'Brien L, Jones DJ. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. 2013;2013(9):CD003826.

  58. Jiang Q, Chen J, Tian F, Liu Z. Silicone gel sheeting for treating hypertrophic scars. Cochrane Database Syst Rev. 2021;9(9):CD013357.

  59. Shi C, Wang C, Liu H, Li Q, Li R, Zhang Y, et al. Selection of appropriate wound dressing for various wounds. Front Bioeng Biotechnol. 2020;8:182.

  60. de Oliveira GV, Nunes TA, Magna LA, Cintra ML, Kitten GT, Zarpellon S, Raposo Do Amaral CM. Silicone versus nonsilicone gel dressings: a controlled trial. Dermatol Surg. 2001;27(8):721-6.

  61. Cronin TD. The use of a molded splint to prevent contracture after split skin grafting on the neck. Probl Sovrem Neirokhirurgii. 1961;27:7-18.

  62. Kischer CW. Alteration of hypertrophic scars induced by mechanical pressure. Arch Dermatol. 1975;111(1):60.

    Article  CAS  PubMed  Google Scholar 

  63. Van den Kerchhove E, Boeckx W, Kochuyt A. Silicone patches as a supplement for pressure therapy to control hypertrophic scarring. J Burn Care Rehabil. 1991;12(4):361-9.

  64. Ward RS. Pressure therapy for the control of hypertrophic scar formation after burn injury. A history and review. J Burn Care Rehabil. 1991;12(3):257-62.

  65. Berman B, Maderal A, Raphael B. Keloids and Hypertrophic Scars: Pathophysiology, Classification, and Treatment. Dermatol Surg. 2017;43 Suppl 1:S3-S18.

  66. Li Z, Dranoff JA, Chan EP, Uemura M, Sévigny J, Wells RG. Transforming growth factor-β and substrate stiffness regulate portal fibroblast activation in culture. Hepatology. 2007;46(4):1246–56.

    Article  CAS  PubMed  Google Scholar 

  67. Renò F. Release and activation of matrix metalloproteinase-9 during in vitro mechanical compression in hypertrophic scars. Arch Dermatol. 2002;138(4):475.

    Article  PubMed  Google Scholar 

  68. Renò F, Grazianetti P, Cannas M. Effects of mechanical compression on hypertrophic scars: prostaglandin E2 release. Burns. 2001;27(3):215-8.

  69. Macintyre L, Baird M. Pressure garments for use in the treatment of hypertrophic scars--a review of the problems associated with their use. Burns. 2006;32(1):10-5.

  70. Poetschke J, Gauglitz GG. Current options for the treatment of pathological scarring. JDDG. 2016;14(5):467–77.

    PubMed  Google Scholar 

  71. Williams F, Knapp D, Wallen M. Comparison of the characteristics and features of pressure garments used in the management of burn scars. Burns. 1998;24(4):329-35.

  72. Yildiz N. A novel technique to determine pressure in pressure garments for hypertrophic burn scars and comfort properties. Burns. 2007;33(1):59-64.

  73. Anzarut A, Olson J, Singh P, Rowe BH, Tredget EE. The effectiveness of pressure garment therapy for the prevention of abnormal scarring after burn injury: a meta-analysis. J Plast Reconstr Aesthet Surg. 2009;62(1):77-84.

  74. Ai J-W, Liu J-T, Pei S-D, Liu Y, Li D-S, Lin H-M, et al. The effectiveness of pressure therapy (15–25 mmHg) for hypertrophic burn scars: a systematic review and meta-analysis. Sci Rep. 2017;7(1):40185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lee K. Onion extract and quercetin induce matrix metalloproteinase-1 in vitro and in vivo. Int J Mol Med. 2010;25:3.

    Article  Google Scholar 

  76. Phan TT, Lim IJ, Sun L, Chan SY, Bay BH, Tan EK, Lee ST. Quercetin inhibits fibronectin production by keloid-derived fibroblasts. Implication for the treatment of excessive scars. J Dermatol Sci. 2003;33(3):192-4.

  77. Ho WS, Ying SY, Chan PC, Chan HH. Use of onion extract, heparin, allantoin gel in prevention of scarring in chinese patients having laser removal of tattoos: a prospective randomized controlled trial. Dermatol Surg. 2006;32(7):891-6.

  78. Sidgwick GP, Mcgeorge D, Bayat A. A comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring. Arch Dermatol Res. 2015;307(6):461–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Chung VQ, Kelley L, Marra D, Jiang SB. Onion extract gel versus petrolatum emollient on new surgical scars: prospective double-blinded study. Dermatol Surg. 2006;32(2):193-7.

  80. Jackson BA, Shelton AJ. Pilot study evaluating topical onion extract as treatment for postsurgical scars. Dermatol Surg. 1999;25(4):267-9.

  81. Yuan X, Shen J, Chen L, Wang L, Yan Q, Zhang J. Onion extract gel is not better than other topical treatments in scar management: a meta-analysis from randomised controlled trails. Int Wound J. 2021;18(3):396–409.

    Article  PubMed  Google Scholar 

  82. Ackermann M, Pabst AM, Houdek JP, Ziebart T, Konerding MA. Priming with proangiogenic growth factors and endothelial progenitor cells improves revascularization in linear diabetic wounds. Int J Mol Med. 2014;33(4):833–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Huang H-P, Zhao W-J, Pu J, He F. Prophylactic negative pressure wound therapy for surgical site infection in obese women undergoing cesarean section: an evidence synthesis with trial sequential analysis. J Matern Fetal Neonat Med. 2021;34(15):2498–505.

    Article  Google Scholar 

  84. Antoniou GA, Onwuka CC, Antoniou SA, Russell D. Meta-analysis and trial sequential analysis of prophylactic negative pressure therapy for groin wounds in vascular surgery. J Vasc Surg. 2019;70(5):1700-10.e6.

    Article  PubMed  Google Scholar 

  85. Du F, Yu Y, Zhou Z, Wang L, Zheng S. Early treatment using fractional CO2 laser before skin suture during scar revision surgery in Asians. J Cosmet Laser Ther. 2018;20(2):102-105.

  86. Ozog DM. A randomized split-scar study of intraoperative treatment of surgical wound edges to minimize scarring. Arch Dermatol. 2011;147(9):1108.

    Article  PubMed  Google Scholar 

  87. Ud-Din S, Wilgus TA, Mcgeorge DD, Bayat A. Pre-emptive priming of human skin improves cutaneous scarring and is superior to immediate and delayed topical anti-scarring treatment post-wounding: a double-blind randomised placebo-controlled clinical trial. Pharmaceutics. 2021;13(4):510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ogawa R. Effectiveness of corticosteroid tapes and plasters for keloids and hypertrophic scars. In: Téot L, Mustoe TA, Middelkoop E, Gauglitz GG, editors. Textbook on scar management: state of the art management and emerging technologies. Cham: Springer International Publishing; 2020. p. 491–6.

    Chapter  Google Scholar 

  89. Roques C, Téot L. The use of corticosteroids to treat keloids: a review. Int J Lower Extremity Wounds. 2008;7(3):137–45.

    Article  Google Scholar 

  90. Diegelmann RF, Bryant CP, Cohen IK. Tissue alpha-globulins in keloid formation. Plast Reconstr Surg. 1977;59(3):418-23.

  91. Hochman B, Locali RF, Matsuoka PK, Ferreira LM. Intralesional triamcinolone acetonide for keloid treatment: a systematic review. Aesthetic Plastic Surg. 2008;32(4):705–9.

    Article  CAS  Google Scholar 

  92. Wu W-S, Wang F-S, Yang KD, Huang C-C, Kuo Y-R. Dexamethasone induction of keloid regression through effective suppression of VEGF expression and keloid fibroblast proliferation. J Invest Dermatol. 2006;126(6):1264–71.

    Article  CAS  PubMed  Google Scholar 

  93. Salem A, Assaf M, Helmy A, Nofal A, Ibrahim S, Eldeeb F, et al. Role of vascular endothelial growth factor in keloids: a clinicopathologic study. Int J Dermatol. 2009;48(10):1071–7.

    Article  PubMed  Google Scholar 

  94. Ogawa R. The Most Current Algorithms for the Treatment and Prevention of Hypertrophic Scars and Keloids: A 2020 Update of the Algorithms Published 10 Years Ago. Plast Reconstr Surg. 2022;149(1):79e-94e.

  95. Abedini R, Sasani P, Mahmoudi HR, Nasimi M, Teymourpour A, Shadlou Z. Comparison of intralesional verapamil versus intralesional corticosteroids in treatment of keloids and hypertrophic scars: A randomized controlled trial. Burns. 2018;44(6):1482-1488.

  96. Saki N, Mokhtari R, Nozari F. Comparing the efficacy of intralesional triamcinolone acetonide with verapamil in treatment of keloids: a randomized controlled trial. Dermatol Pract Concept. 2019;9(1):4–9.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Muneuchi G, Suzuki S, Onodera M, Ito O, Hata Y, Igawa HH. Long-term outcome of intralesional injection of triamcinolone acetonide for the treatment of keloid scars in Asian patients. Scand J Plast Reconst Surg Hand Surg. 2006;40(2):111–6.

    Article  Google Scholar 

  98. Trisliana Perdanasari A, Lazzeri D, Su W, ** W, Zheng Z, Ke L, et al. Recent developments in the use of intralesional injections keloid treatment. Arch Plast Surg. 2014;41(06):620–9.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Kafka M, Collins V, Kamolz L-P, Rappl T, Branski LK, Wurzer P. Evidence of invasive and noninvasive treatment modalities for hypertrophic scars: a systematic review. Wound Repair Regen. 2017;25(1):139–44.

    Article  PubMed  Google Scholar 

  100. Ogawa R, Akita S, Akaishi S, Aramaki-Hattori N, Dohi T, Hayashi T, et al. Diagnosis and treatment of keloids and hypertrophic scars: Japan Scar Workshop Consensus Document 2018. Burns Trauma. 2019;7:1.

    Article  Google Scholar 

  101. Goutos I, Ogawa R. Steroid tape: a promising adjunct to scar management. Scars Burns Healing. 2017;3:205951311769093.

    Article  Google Scholar 

  102. te Hayashi T, Furukawa H, Oyama A, Funayama E, Saito A, Murao N, Yamamoto Y. A new uniform protocol of combined corticosteroid injections and ointment application reduces recurrence rates after surgical keloid/hypertrophic scar excision. Dermatol Surg. 2012;38(6):893-7.

  103. Wigmore PM, Mustafa S, El-Beltagy M, Lyons L, Umka J, Bennett G. Effects of 5-FU. Adv Exp Med Biol. 2010;678:157-64.

  104. Kontochristopoulos G, Stefanaki C, Panagiotopoulos A, Stefanaki K, Argyrakos T, Petridis A, Katsambas A. Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study. J Am Acad Dermatol. 2005;52(3 Pt 1):474-9.

  105. Huang L, Cai YJ, Lung I, Leung BC, Burd A. A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro. J Plast Reconstr Aesthet Surg. 2013;66(9):e251-9.

  106. Hietanen K, Järvinen T, Huhtala H, Tolonen T, Kuokkanen H, Kaartinen I. Treatment of keloid scars with intralesional triamcinolone and 5-fluorouracil injections: a randomized controlled trial. J Plast Reconstruct Aesthet Surg. 2019;72(1):4–11.

    Article  CAS  Google Scholar 

  107. Sharma S, Vinay K, Bassi R. Treatment of Small Keloids Using Intralesional 5-fluorouracil and Triamcinolone Acetonide versus Intralesional Bleomycin and Triamcinolone Acetonide. J Clin Aesthet Dermatol. 2021;14(3):17-21.

  108. Gupta S, Kalra A. Efficacy and safety of intralesional 5-fluorouracil in the treatment of keloids. Dermatology. 2002;204(2):130-2.

  109. Nanda S, Reddy BS. Intralesional 5-fluorouracil as a treatment modality of keloids. Dermatol Surg. 2004;30(1):54-6; discussion 56-7.

  110. Saha AK, Mukhopadhyay M. A comparative clinical study on role of 5-flurouracil versus triamcinolone in the treatment of keloids. Ind J Surg. 2012;74(4):326–9.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Berman B, Kaufman J. Pilot study of the effect of postoperative imiquimod 5% cream on the recurrence rate of excised keloids. J Am Acad Dermatol. 2002;47(4 Suppl):S209-11.

  112. Berman B, Villa A. Imiquimod 5% cream for keloid management. Dermatol Surg. 2003;29(10):1050–1.

    PubMed  Google Scholar 

  113. Schön MP, Schön M. Imiquimod: mode of action. Br J Dermatol. 2007;157:8–13.

    Article  PubMed  Google Scholar 

  114. Shin JY, Yun SK, Roh SG, Lee NH, Yang KM. Efficacy of 2 Representative Topical Agents to Prevent Keloid Recurrence After Surgical Excision. J Oral Maxillofac Surg. 2017;75(2):401.e1-401.e6.

  115. Berman B, Harrison-Balestra C, Perez OA, Viera M, Villa A, Zell D, Ramirez C. Treatment of keloid scars post-shave excision with imiquimod 5% cream: A prospective, double-blind, placebo-controlled pilot study. J Drugs Dermatol. 2009;8(5):455-8.

  116. Cação FM, Tanaka V, Messina MC. Failure of imiquimod 5% cream to prevent recurrence of surgically excised trunk keloids. Dermatol Surg. 2009;35(4):629-33.

  117. Klotz T, Munn Z, Aromataris EC, Greenwood JE. Imiquimod to prevent keloid recurrence postexcision: A systematic review and meta-analysis. Wound Repair Regen. 2020;28(1):145–56.

    Article  PubMed  Google Scholar 

  118. Fahie S, Cassagnol M. Verapamil. London: BTI-StatPearls: StatPearls Publishing; 2022.

    Google Scholar 

  119. Doong H, Dissanayake S, Gowrishankar TR, LaBarbera MC, Lee RC. The 1996 Lindberg Award. Calcium antagonists alter cell shape and induce procollagenase synthesis in keloid and normal human dermal fibroblasts. J Burn Care Rehabil. 1996;17(6 Pt 1):497-514.

  120. Srivastava S, Kumari H, Singh A. Comparison of fractional CO2 laser, verapamil, and triamcinolone for the treatment of keloid. Adv Wound Care. 2019;8(1):7–13.

    Article  Google Scholar 

  121. Li Z, ** Z. Comparative effect and safety of verapamil in keloid and hypertrophic scar treatment: a meta-analysis. Ther Clin Risk Manage. 2016;12:1635–41.

    Article  Google Scholar 

  122. McGinty S, Siddiqui WJ. Keloid. London: BTI-StatPearls: StatPearls Publishing; 2021.

    Google Scholar 

  123. Arima J, Dohi T, Kuribayashi S, Akaishi S, Ogawa R. Z-plasty and Postoperative Radiotherapy for Anterior Chest Wall Keloids: An Analysis of 141 Patients. Plast Reconstr Surg Glob Open. 2019;7(3):e2177.

  124. Shin JY, Lee JW, Roh SG, Lee NH, Yang KM. A Comparison of the Effectiveness of Triamcinolone and Radiation Therapy for Ear Keloids after Surgical Excision: A Systematic Review and Meta-Analysis. Plast Reconstr Surg. 2016;137(6):1718-1725.

  125. Apfelberg DB, Maser MR, Dds HL, White D, Weston J. Preliminary results of argon and carbon dioxide laser treatment of keloid scars. Lasers Surg Med. 1984;4(3):283–90.

    Article  CAS  PubMed  Google Scholar 

  126. Preissig J, Hamilton K, Markus R. Current laser resurfacing technologies: a review that delves beneath the surface. Semin Plast Surg. 2012;26(03):109–16.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Makboul M, Makboul R, Abdelhafez AH, Hassan SS, Youssif SM. Evaluation of the effect of fractional CO 2 laser on histopathological picture and TGF-β1 expression in hypertrophic scar. J Cosmet Dermatol. 2014;13(3):169–79.

    Article  PubMed  Google Scholar 

  128. Lee SJ, Suh DH, Lee JM, Song KY, Ryu HJ. Dermal remodeling of burn scar by fractional CO2 laser. Aesthetic Plast Surg. 2016;40(5):761–8.

    Article  PubMed  Google Scholar 

  129. Patel SP, Nguyen HV, Mannschreck D, Redett RJ, Puttgen KB, Stewart FD. Fractional CO2 laser treatment outcomes for pediatric hypertrophic burn scars. J Burn Care Res. 2019;40(4):386–91.

    Article  PubMed  Google Scholar 

  130. Azzam OA, Bassiouny DA, El-Hawary MS, El Maadawi ZM, Sobhi RM, El-Mesidy MS. Treatment of hypertrophic scars and keloids by fractional carbon dioxide laser: a clinical, histological, and immunohistochemical study. Lasers Med Sci. 2016;31(1):9–18.

    Article  CAS  PubMed  Google Scholar 

  131. Poetschke J, Dornseifer U, Clementoni MT, Reinholz M, Schwaiger H, Steckmeier S, et al. Ultrapulsed fractional ablative carbon dioxide laser treatment of hypertrophic burn scars: evaluation of an in-patient controlled, standardized treatment approach. Lasers Med Sci. 2017;32(5):1031–40.

    Article  PubMed  Google Scholar 

  132. Levi B, Ibrahim A, Mathews K, Wojcik B, Gomez J, Fagan S, et al. The use of CO2 fractional photothermolysis for the treatment of burn scars. J Burn Care Res. 2016;37(2):106–14.

    Article  PubMed  Google Scholar 

  133. Liu A, Moy RL, Victor Ross E, Hamzavi I, Ozog DM. Pulsed dye laser and pulsed dye laser-mediated photodynamic therapy in the treatment of dermatologic disorders. Dermatol Surg. 2012;38(3):351–66.

    Article  CAS  PubMed  Google Scholar 

  134. Artzi O, Friedman O, Al-Niaimi F, Wolf Y, Mehrabi JN. Mitigation of postsurgical scars using lasers: a review. Plast Reconstr Surg Glob Open. 2020;8(4): e2746.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Pongcharoen P, Pongcharoen B, Disphanurat W. The effectiveness of a 595 nm pulsed-dye-laser in the treatment of surgical scars following a knee arthroplasty. J Cosmet Laser Ther. 2019;21(6):352–6.

    Article  PubMed  Google Scholar 

  136. Nouri K, Rivas MP, Stevens M, Ballard CJ, Singer L, Ma F, et al. Comparison of the effectiveness of the pulsed dye laser 585 nm versus 595 nm in the treatment of new surgical scars. Lasers Med Sci. 2009;24(5):801–10.

    Article  PubMed  Google Scholar 

  137. Koike S, Akaishi S, Nagashima Y, Dohi T, Hyakusoku H, Ogawa R. Nd:YAG laser treatment for keloids and hypertrophic scars: an analysis of 102 cases. Plast Reconstr Surg Glob Open. 2014;2(12): e272.

    Article  PubMed  Google Scholar 

  138. Pan L, Qin H, Li C, Zhang G, Yang L, Zhang L. Efficacy of the neodymium-doped yttrium aluminum garnet laser in the treatment of keloid and hypertrophic scars: a systematic review and meta-analysis. Aesthetic Plast Surg. 2022.

  139. Li K, Nicoli F, Cui C, ** WJ, Al-Mousawi A, Zhang Z, et al. Treatment of hypertrophic scars and keloids using an intralesional 1470 nm bare-fibre diode laser: a novel efficient minimally-invasive technique. Sci Rep. 2020;10(1):21694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Lin JY, Warger WC, Izikson L, Anderson RR, Tannous Z. A prospective, randomized controlled trial on the efficacy of fractional photothermolysis on scar remodeling. Lasers Surg Med. 2011;43(4):265–72.

    Article  PubMed  Google Scholar 

  141. Shin J, Cho JT, Park SI, Jung SN. Combination therapy using non-ablative fractional laser and intralesional triamcinolone injection for hypertrophic scars and keloids treatment. Int Wound J. 2019;16(6):1450–6.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Verhaeghe E, Ongenae K Fau - Bostoen J, Bostoen J Fau - Lambert J, Lambert J. Nonablative fractional laser resurfacing for the treatment of hypertrophic scars: a randomized controlled trial. 2013.

  143. Tierney E, Mahmoud BH, Srivastava D, Ozog D, Kouba DJ. Treatment of surgical scars with nonablative fractional laser versus pulsed dye laser: a randomized controlled trial. Dermatol Surg. 2009;35(8):1172-80.

  144. Anderson RR, Donelan MB, Hivnor C, Greeson E, Ross EV, Shumaker PR, et al. Laser treatment of traumatic scars with an emphasis on ablative fractional laser resurfacing. JAMA Dermatol. 2014;150(2):187.

    Article  PubMed  Google Scholar 

  145. Seago M, Shumaker PR, Spring LK, Alam M, Al-Niaimi F, Rox Anderson R, et al. Laser treatment of traumatic scars and contractures: 2020 International Consensus recommendations. Lasers Surg Med. 2020;52(2):96–116.

    Article  PubMed  Google Scholar 

  146. Conejo-Mir JS, Corbi R, Linares M. Carbon dioxide laser ablation associated with interferon alfa-2b injections reduces the recurrence of keloids. J Am Acad Dermatol. 1998;39(6):1039-40.

  147. Cavalié M, Sillard L, Montaudié H, Bahadoran P, Lacour J-P, Passeron T. Treatment of keloids with laser-assisted topical steroid delivery: a retrospective study of 23 cases. Dermatol Ther. 2015;28(2):74–8.

    Article  PubMed  Google Scholar 

  148. Sabry HH, Abdel Rahman SH, Hussein MS, Sanad RR, Abd El Azez TA. The Efficacy of Combining Fractional Carbon Dioxide Laser With Verapamil Hydrochloride or 5-Fluorouracil in the Treatment of Hypertrophic Scars and Keloids: A Clinical and Immunohistochemical Study. Dermatol Surg. 2019;45(4):536-546.

  149. Ouyang H-W, Li G-F, Lei Y, Gold MH, Tan J. Comparison of the effectiveness of pulsed dye laser vs pulsed dye laser combined with ultrapulse fractional CO2 laser in the treatment of immature red hypertrophic scars. J Cosmet Dermatol. 2018;17(1):54–60.

    Article  PubMed  Google Scholar 

  150. Cohen JL, Geronemus R. Safety and efficacy evaluation of pulsed dye laser treatment, CO2 ablative fractional resurfacing, and combined treatment for surgical scar clearance. J Drugs Dermatol. 2016;15(11):1315–9.

    PubMed  Google Scholar 

  151. Zhang J, Zhou S, **a Z, Peng Z, Cheng X, Yang X, et al. 595-nm pulsed dye laser combined with fractional CO2 laser reduces hypertrophic scar through down-regulating TGFβ1 and PCNA. Lasers Med Sci. 2021;36(8):1625–32.

    Article  PubMed  Google Scholar 

  152. Lee YI, Kim J, Yang CE, Hong JW, Lee WJ, Lee JH. Combined therapeutic strategies for keloid treatment. Dermatol Surg. 2019;45(6):802–10.

    Article  CAS  PubMed  Google Scholar 

  153. Verma KK, Garg T, Raj T. Carbon dioxide leaser for the treatment of keloids. Indian J Dermatol. 2002;47(2):91.

    Google Scholar 

  154. Morelli Coppola M, Salzillo R, Segreto F, Persichetti P. Triamcinolone acetonide intralesional injection for the treatment of keloid scars: patient selection and perspectives. Clin Cosmet Investig Dermatol. 2018;11:387–96.

    Article  PubMed  PubMed Central  Google Scholar 

  155. Wang J, Wu J, Xu M, Gao Q, Chen B, Wang F, et al. Combination therapy of refractory keloid with ultrapulse fractional carbon dioxide (CO2). Dermatol Ther. 2020;33(6):14359.

    Article  Google Scholar 

  156. Forbat E, Al-Niaimi F. Treatment of striae distensae: an evidence-based approach. J Cosmet Laser Ther. 2019;21(1):49–57.

    Article  PubMed  Google Scholar 

  157. Yun PL, Tachihara R, Anderson RR. Efficacy of erbium:yttrium-aluminum-garnet laser-assisted delivery of topical anesthetic. J Am Acad Dermatol. 2002;47(4):542-7.

  158. Braun SA, Schrumpf H, Buhren BA, Homey B, Gerber PA. Laser-assisted drug delivery: mode of action and use in daily clinical practice. JDDG. 2016;14(5):480–8.

    PubMed  Google Scholar 

  159. Waibel JS, Wulkan AJ, Shumaker PR. Treatment of hypertrophic scars using laser and laser assisted corticosteroid delivery. Lasers Surg Med. 2013;45(3):135–40.

    Article  PubMed  Google Scholar 

  160. Abd El-Dayem DH, Nada HA, Hanafy NS, Elsaie ML. Laser-assisted topical steroid application versus steroid injection for treating keloids: a split side study. J Cosmet Dermatol. 2021;20(1):138–42.

    Article  PubMed  Google Scholar 

  161. Sabry HH, Ibrahim EA, Hamed AM. Assessment of laser-assisted delivery vs intralesional injection of botulinum toxin A in treatment of hypertrophic scars and keloids. Dermatol Ther. 2020;33:6.

    Article  Google Scholar 

  162. Park JH, Chun JY, Lee JH. Laser-assisted topical corticosteroid delivery for the treatment of keloids. Lasers Med Sci. 2017;32(3):601–8.

    Article  PubMed  Google Scholar 

  163. Waibel JS, Wulkan AJ, Rudnick A, Daoud A. Treatment of Hypertrophic Scars Using Laser-Assisted Corticosteroid Versus Laser-Assisted 5-Fluorouracil Delivery. Dermatol Surg. 2019;45(3):423-430.

  164. Truong K, Prasidha I, Wain T. A systematic review of randomised controlled trials investigating laser assisted drug delivery for the treatment of keloid and hypertrophic scars. Lasers Med Sci. 2022;37(1):47–59.

    Article  PubMed  Google Scholar 

  165. Mankowski P, Kanevsky J, Tomlinson J, Dyachenko A, Luc M. Optimizing Radiotherapy for Keloids: A Meta-Analysis Systematic Review Comparing Recurrence Rates Between Different Radiation Modalities. Ann Plast Surg. 2017;78(4):403-411.

  166. Miles OJ, Zhou J, Paleri S, Fua T, Ramakrishnan A. Chest keloids: effect of surgical excision and adjuvant radiotherapy on recurrence, a systematic review and meta-analysis. ANZ J Surg. 2021;91(6):1104–9.

    Article  PubMed  Google Scholar 

  167. Shen J, Lian X, Sun Y, Wang X, Hu K, Hou X, et al. Hypofractionated electron-beam radiation therapy for keloids: retrospective study of 568 cases with 834 lesions. J Radiat Res. 2015;56(5):811–7.

    Article  PubMed  PubMed Central  Google Scholar 

  168. Ji J, Tian Y, Zhu Y-Q, Zhang L-Y, Ji S-J, Huan J, et al. Ionizing irradiation inhibits keloid fibroblast cell proliferation and induces premature cellular senescence. J Dermatol. 2015;42(1):56–63.

    Article  CAS  PubMed  Google Scholar 

  169. Liu EK, Cohen RF, Chiu ES. Radiation therapy modalities for keloid management: a critical review. J Plast Reconstr Aesthet Surg. 2022.

  170. Ogawa R, Akaishi S, Kuribayashi S, Miyashita T. Keloids and hypertrophic scars can now be cured completely: recent progress in our understanding of the pathogenesis of keloids and hypertrophic scars and the most promising current therapeutic strategy. J Nippon Med School. 2016;83(2):46–53.

    Article  CAS  Google Scholar 

  171. Kal HB, Veen RE. Biologically effective doses of postoperative radiotherapy in the prevention of keloids. Strahlenther Onkol. 2005;181(11):717–23.

    Article  PubMed  Google Scholar 

  172. Wang LZ, Ding JP, Yang MY, Chen B. Forty-five cases of chest keloids treated with subcutaneous super-tension-reduction suture combined with postoperative electron-beam irradiation. Dermatol Surg. 2014;40(12):1378–84.

    Article  CAS  PubMed  Google Scholar 

  173. Pashazadeh A, Boese A, Friebe M. Radiation therapy techniques in the treatment of skin cancer: an overview of the current status and outlook. J Dermatolog Treat. 2019;30(8):831–9.

    Article  CAS  PubMed  Google Scholar 

  174. Bijlard E, Verduijn GM, Harmeling JX, Dehnad H, Niessen FB, Meijer OWM, et al. Optimal high-dose-rate brachytherapy fractionation scheme after keloid excision: a retrospective multicenter comparison of recurrence rates and complications. Int J Radiat Oncol Biol Phys. 2018;100(3):679–86.

    Article  PubMed  Google Scholar 

  175. Guida S, Pellacani G, Bencini PL. Picosecond laser treatment of atrophic and hypertrophic surgical scars: In vivo monitoring of results by means of 3D imaging and reflectance confocal microscopy. Skin Res Technol. 2019.

  176. Gold MH, Nestor MS, Berman B, Goldberg D. Assessing keloid recurrence following surgical excision and radiation. Burns Trauma. 2020;8:tkaa01.

    Article  Google Scholar 

  177. Cognetta AB, Wolfe CM, Goldberg DJ, Hong HG. Practice and educational gaps in radiation therapy in dermatology. Dermatol Clin. 2016;34(3):319–33.

    Article  CAS  PubMed  Google Scholar 

  178. Song C, Wu HG, Chang H, Kim IH, Ha SW. Adjuvant single-fraction radiotherapy is safe and effective for intractable keloids. J Radiat Res. 2014;55(5):912–6.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Emad M, Omidvari S, Dastgheib L, Mortazavi A, Ghaem H. Surgical excision and immediate postoperative radiotherapy versus cryotherapy and intralesional steroids in the management of keloids: a prospective clinical trial. Med Princ Pract. 2010;19(5):402–5.

    Article  PubMed  Google Scholar 

  180. Jones ME, Ganzer CA, Bennett D, Finizio A. Surgical excision of keloids followed by in-office superficial radiation therapy: prospective study examining clinicaloOutcomes. Plast Reconstr Surg Glob Open. 2019;7(5): e2212.

    Article  PubMed  PubMed Central  Google Scholar 

  181. Berman B, Nestor MS, Gold MH, Goldberg DJ, Weiss ET, Raymond I. A retrospective registry study evaluating the long-term efficacy and safety of superficial radiation therapy following excision of keloid scars. J Clin Aesthet Dermatol. 2020;13(10):12–6.

    PubMed  PubMed Central  Google Scholar 

  182. Nestor MS, Berman B, Goldberg D, Cognetta AB, Gold M, Roth W, et al. Consensus guidelines on the use of superficial radiation therapy for treating nonmelanoma skin cancers and keloids. J Clin Aesthet Dermatol. 2019;12(2):12–8.

    PubMed  PubMed Central  Google Scholar 

  183. Li L, Yuan C, Zhang X, Wang B, Yan Y. Superficial X-ray-induced hyperpigmentation in postoperative keloid radiotherapy: a study of 70 keloids to identify clinical features and risk factors. J Cosmet Dermatol. 2021;20(9):2880–6.

    Article  PubMed  Google Scholar 

  184. Ogawa R, Yoshitatsu S, Yoshida K, Miyashita T. Is radiation therapy for keloids acceptable? The risk of radiation-induced carcinogenesis. Plast Reconstr Surg. 2009;124(4):1196-1201.

  185. Har-Shai Y, Amar M, Sabo E. Intralesional cryotherapy for enhancing the involution of hypertrophic scars and keloids. Plast Reconstr Surg. 2003;111(6):1841-52.

  186. Zouboulis CC. Outcomes of cryosurgery in keloids and hypertrophic scars. Arch Dermatol. 1993;129(9):1146.

    Article  CAS  PubMed  Google Scholar 

  187. O’Boyle CP, Shayan-Arani H, Hamada MW. Intralesional cryotherapy for hypertrophic scars and keloids: a review. Scars Burns Healing. 2017;3:205951311770216.

    Article  Google Scholar 

  188. Rusciani L, Rossi G, Bono R. Use of cryotherapy in the treatment of keloids. J Dermatol Surg Oncol. 1993 Jun;19(6):529-34.

  189. van Leeuwen MC, Bulstra AE, Ket JC, Ritt MJ, van Leeuwen PA, Niessen FB. Intralesional cryotherapy for the treatment of keloid scars: evaluating effectiveness. 2015.

  190. Har-Shai Y, Sabo E Fau - Rohde E, Rohde E Fau - Hyams M, Hyams M Fau - Assaf C, Assaf C Fau - Zouboulis CC, Zouboulis CC. Intralesional cryosurgery enhances the involution of recalcitrant auricular keloids: a new clinical approach supported by experimental studies. 2006.

  191. Zhang X, Wu Q, Wei M, Deng X, Gu C, Wang Z. Oxaliplatin versus mitomycin C in HIPEC for peritoneal metastasis from colorectal cancer: a systematic review and meta-analysis of comparative studies. Int J Colorect Dis. 2020;35(10):1831–9.

    Article  Google Scholar 

  192. Mearza AA, Aslanides IM. Uses and complications of mitomycin C in ophthalmology. Expert Opin Drug Saf. 2007;6(1):27-32.

  193. Simman R, Alani H, Williams F. Effect of mitomycin C on keloid fibroblasts: an in vitro study. Ann Plast Surg. 2003;50(1):71-6.

  194. Sanders KW, Gage-White L, Stucker FJ. Topical mitomycin C in the prevention of keloid scar recurrence. Arch Facial Plast Surg. 2005;7(3):172-5.

  195. Mandour Y, Bake H, Mofty E, Ramadan E, Gomaa M, Akl E, Elrefae A. Topical versus interlesional mitomycin C in auricular keloids. Acta Otorrinolaringol Esp (Engl Ed). 2021;72(5):280-287.

  196. Seo S-H, Sung H-W. Treatment of keloids and hypertrophic scars using topical and intralesional mitomycin C. J Eur Acad Dermatol Venereol. 2012;26(5):634–8.

    Article  CAS  PubMed  Google Scholar 

  197. Stewart Iv CE, Kim JY. Application of mitomycin-C for head and neck keloids. Otolaryngol Head Neck Surg. 2006;135(6):946–50.

    Article  Google Scholar 

  198. Frampton JE, Easthope SE. Botulinum toxin A (Botox Cosmetic): a review of its use in the treatment of glabellar frown lines. Am J Clin Dermatol. 2003;4(10):709-25.

  199. Yang W, Li G. The Safety and efficacy of botulinum toxin type A injection for postoperative scar prevention: a systematic review and meta-analysis. J Cosmet Dermatol. 2020;19(4):799–808.

    Article  PubMed  Google Scholar 

  200. Dai X, Lei TC. Botulinum toxin A promotes the transdifferentiation of primary keloid myofibroblasts into adipocyte-like cells. Basic Clin Pharmacol Toxicol. 2021;129(6):462–9.

    Article  CAS  PubMed  Google Scholar 

  201. Ismail SA, Mohammed NHK, Sotohy M, Abou-Taleb DAE. Botulinum toxin type A versus 5-fluorouracil in treatment of keloid. Arch Dermatol Res. 2021;313(7):549–56.

    Article  CAS  PubMed  Google Scholar 

  202. Cho SB, Lee SJ, Cho S, Oh SH, Chung WS, Kang JM, et al. Non-ablative 1550-nm erbium-glass and ablative 10 600-nm carbon dioxide fractional lasers for acne scars: a randomized split-face study with blinded response evaluation. J Eur Acad Dermatol Venereol. 2010;24(8):921–5.

    Article  CAS  PubMed  Google Scholar 

  203. Liu XG, Zhang D. Evaluation of efficacy of corticosteroid and corticosteroid combined with botulinum toxin type A in the treatment of keloid and hypertrophic scars: a meta-analysis. Aesthetic Plast Surg. 2021;45(6):3037–44.

    Article  PubMed  Google Scholar 

  204. Sun P, Lu X, Zhang H, Hu Z. The efficacy of drug injection in the treatment of pathological scar: a network meta-analysis. Aesthetic Plast Surg. 2021;45(2):791–805.

    Article  PubMed  Google Scholar 

  205. Bi M, Sun P, Li D, Dong Z, Chen Z. Intralesional injection of botulinum toxin type A compared with intralesional injection of corticosteroid for the treatment of hypertrophic scar and keloid: a systematic review and meta-analysis. Med Sci Monit. 2019;25:2950–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Wilson AM. Eradication of keloids: Surgical excision followed by a single injection of intralesional 5-fluorouracil and botulinum toxin. Can J Plast Surg. 2013;21(2):87–91.

    Article  PubMed  PubMed Central  Google Scholar 

  207. Laurent TC, Fraser JR. Hyaluronan. 1992.

  208. A DIS. Ear Keloid Treated with Infiltrated non-cross-linked hyaluronic acid and cortisone therapy. 2016;1791–7549.

  209. Alaish SM, Yager DR, Diegelmann RF, Cohen IK. Hyaluronic acid metabolism in keloid fibroblasts. J Pediatr Surg. 1995;30(7):949-52.

  210. Sidgwick GP, Iqbal SA, Bayat A. Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin. Exp Dermatol. 2013;22(5):377–9.

    Article  CAS  PubMed  Google Scholar 

  211. Aggarwal A, Ravikumar BC, Vinay KN, Raghukumar S, Yashovardhana DP. A comparative study of various modalities in the treatment of keloids. Int J Dermatol. 2018;57(10):1192–200.

    Article  CAS  PubMed  Google Scholar 

  212. Wu DC, Goldman MP, Wat H, Chan HHL. A systematic review of picosecond laser in dermatology: evidence and recommendations. Lasers Surg Med. 2021;53(1):9–49.

    Article  PubMed  Google Scholar 

  213. Choi YJ, Kim JY, Nam JH, Lee GY, Kim WS. Clinical outcome of 1064-nm picosecond neodymium-doped yttrium aluminium garnet laser for the treatment of hypertrophic scars. 2018;2018:1476–80.

  214. Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130–9.

    Article  PubMed  Google Scholar 

  215. Wong AJS, Song EJ. Dupilumab as an adjuvant treatment for keloid-associated symptoms. JAAD Case Rep. 2021;13:73–4.

    Article  PubMed  PubMed Central  Google Scholar 

  216. Peterson DM, Damsky WE, Vesely MD. Treatment of lichen sclerosus and hypertrophic scars with dupilumab. JAAD Case Rep. 2022;23:76–8.

    Article  PubMed  PubMed Central  Google Scholar 

  217. Luk K, Fakhoury J, Ozog D. Nonresponse and progression of diffuse keloids to dupilumab therapy. J Drugs Dermatol. 2022;21(2):197–9.

    Article  PubMed  Google Scholar 

  218. Tan A, Martinez Luna O, Glass DA. Pentoxifylline for the prevention of postsurgical keloid recurrence. Dermatol Surg. 2020;46(10):1353–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Berman B, Duncan MR. Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin. Br J Dermatol. 1990;123(3):339–46.

    Article  CAS  PubMed  Google Scholar 

  220. Wong TW, Lee JY, Sheu HM, Chao SC. Relief of pain and itch associated with keloids on treatment with oxpentifylline. Br J Dermatol. 1999;140(4):771–2.

    CAS  PubMed  Google Scholar 

  221. Serag-Eldin YMA, Mahmoud WH, Gamea MM, Hegab DS. Intralesional pentoxifylline, triamcinolone acetonide, and their combination for treatment of keloid scars. J Cosmet Dermatol. 2021;20(10):3330–40.

    Article  PubMed  Google Scholar 

  222. Darakhshan S, Pour AB. Tranilast: a review of its therapeutic applications. Pharmacol Res. 2015;91:15–28.

    Article  CAS  PubMed  Google Scholar 

  223. Isaji M, Nakajoh M, Naito J. Selective inhibition of collagen accumulation by N-(3,4-dimethoxycinnamoyl)anthranilic acid (N-5’) in granulation tissue. Biochem Pharmacol. 1987;36(4):469–74.

    Article  CAS  PubMed  Google Scholar 

  224. Nanba K, Oura T, Soeda S, Sioya N, Tsukada S, Hanaoka K. Clinical evaluation of tranilast for keloid and hypertrophic scarring: optimal dose finding study in a double blind study. Nessho. 1992;18:30–45.

    Google Scholar 

  225. Nakamura K, Irie H, Inoue M, Mitani H, Sunami H, Sano S. Factors affecting hypertrophic scar development in median sternotomy incisions for congenital cardiac surgery. J Am Coll Surg. 1997;185(3):218–23.

    Article  CAS  PubMed  Google Scholar 

  226. Kim J, Lee YI, Lee JH. Efficacy and safety of oral tranilast for keloid scar: a single-center, retrospective observational study.2020;72(1):416.

  227. El-Hamid El-Azhary EA, Abd Al-Salam FM, El-Hafiz HSA, Maghraby HM. Fractional carbon dioxide (CO). Dermatol Pract Concept. 2022;12(2): e2022072.

    PubMed  PubMed Central  Google Scholar 

  228. Kasper B, Baumgarten C, Garcia J, Bonvalot S, Haas R, Haller F, et al. An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG). Ann Oncol. 2017;28(10):2399–408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Author notes

  1. Fabio Stefano Frech, Loren Hernandez and Rebecca Urbonas contributed equally to the article.

Authors and Affiliations

  1. Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 1150 Northwest 14th Street, Miami, FL, 33136, USA

    Fabio Stefano Frech, Loren Hernandez, Ghufran Abo Zaken & Keyvan Nouri

  2. Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA

    Rebecca Urbonas

  3. Nova Southeastern University, Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

    Isabella Dreyfuss

Authors
  1. Fabio Stefano Frech
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  2. Loren Hernandez
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  3. Rebecca Urbonas
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  4. Ghufran Abo Zaken
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  5. Isabella Dreyfuss
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  6. Keyvan Nouri
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Corresponding author

Correspondence to Fabio Stefano Frech.

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The authors received no funding for the completion of this review.

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Authors’ contributions

F.S.F., R.U., L.H., and K.N. developed the main conceptual ideas and proof outline. F.S.F. and R.U. worked out almost all the technical details within the manuscript. F.S.F., R.U., and L.H. wrote the manuscript with the support of G.A.Z. and I.D. Tables were devised and created by R.U. and F.S.F. K.N. supervised the manuscript preparation. All authors approved the final version of the submitted manuscript.

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Frech, F.S., Hernandez, L., Urbonas, R. et al. Hypertrophic Scars and Keloids: Advances in Treatment and Review of Established Therapies. Am J Clin Dermatol 24, 225–245 (2023). https://doi.org/10.1007/s40257-022-00744-6

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